The long-term goal of the proposed research is to elucidate, quantitate and where possible delineate the temporal contribution of chemical factors in the local regulation of blood flow. The proposed studies also have the objective of quantitatively determining the contribution of myogenic factors to active hyperemia in skeletal muscle. Specifically, we propose through the use of an improved bioassay system in conjunction with specific pharmacologic blockers, to precisely define the nature of the substance(s) that appear in coronary sinus blood in vasoactive quantities during coronary sinus blood in vasoactive quantities during coronary reactive hyperemia. Moreover, we propose to determine whether this substance(s) also appears in sinus blood during hypoxic dilation. In isolated Ringer's perfused guinea pig hearts we plan to chemically analyze the sinus effluent for AMP during reactive and hypoxic hyperemias. We propose to determine if hypoxic and/or hypercapnic dilation in skin, skeletal muscle, and kidney are partly mediated by the release of adenosine and/or adenine nucleotides, prostaglandins or histamine. We propose to collect and chemically characterize skeletal muscle lymph both during rest and activity. We propose to examine the role of myogenic factors in the mediation of exercise hyperemia.